Resistance of shigellae to ampicillin and other antibiotics: South Bronx, New York (1971 and 1972)

Lerman, Stephen J.; Waller, J. M.; Simms, David H.

doi:10.1016/s0022-3476(73)80286-0

Cited by 11 publications

(5 citation statements)

References 3 publications

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“…Pivmecillinam, the pivaloyloxymethyl ester of mecillinam, is well absorbed from the gastrointestinal tract and during or after absorption is rapidly hydrolyzed to mecillinam. The hydrolysis is catalyzed by enzymes present in blood and in many tissues, including intestinal mucosa (8,11,13 tions and cultures were repeated daily for 7 consecutive days after the onset of therapy. All specimens were plated on MacConkey and shigella-salmonella agar.…”

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Comparative efficacies of pivmecillinam and ampicillin in acute shigellosis

Kabir¹,

Rahaman²,

Ahmed³

et al. 1984

Antimicrob Agents Chemother

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The clinical efficacies of pivmecillinam and ampicillin were compared in a randomized double-blind trial in the treatment of acute shigellosis. Of In developing countries, shigellosis is a disease that causes severe morbidity, even mortality, in young children. Clinical studies have shown that appropriate antibiotic therapy decreases the duration of fever, diarrhea, abdominal pain, and excretion of Shigella organisms in the stool (4, 5, 7). Although mecillinam is highly active against Shigella strains in vitro (6, 9), its usefulness in the treatment of shigellosis is limited because of the need for parenteral delivery. Pivmecillinam, the pivaloyloxymethyl ester of mecillinam, is well absorbed from the gastrointestinal tract and during or after absorption is rapidly hydrolyzed to mecillinam. The hydrolysis is catalyzed by enzymes present in blood and in many tissues, including intestinal mucosa (8,11,13 tions and cultures were repeated daily for 7 consecutive days after the onset of therapy. All specimens were plated on MacConkey and shigella-salmonella agar. Typical lactosenegative colonies were transferred to Kligler iron agar and were differentiated with polyvalent typing sera and with selective biochemical tests. In vitro antibiotic disk sensitivities were performed on all Shigella isolates, using the Bauer-Kirby method (1).Mecillinam disks containing 33 jig of drug were obtained from Leo Pharmaceuticals; a clear zone of more than 16 mm in diameter was used to indicate sensitivity. The leukocyte count and urinalysis were done for each patient on the day of admission and on day 7 of hospitalization. Patients were asked to return 2 weeks after discharge, at which time microscopic examination, a stool culture, and complete blood count were performed. Careful attention was given to adverse effects during therapy, such as urticaria, penicillin hypersensitivity, nausea, and vomiting.Treatment groups were compared with respect to the number of stools per 24 h; duration of bloody diarrhea, abdominal pain, fever, and tenesmus; and positive stool cultures. Diarrhea was defined as three or more stools per day. Statistical significance was done by Student's t test. RESULTSStool cultures were positive for shigella in 44 patients. Of these, 22 patients received pivmecillinam and 22 patients received ampicillin. The mean durations of prehospitalization illness were 3.8 days in patients treated with pivmecillinam and 3.5 days in patients treated with ampicillin. The most common presenting symptoms were passage of bloody mucoid stool (100%), abdominal pain or cramps (93%), tenesmus (93%), and fever (70%). On physical examination, 41% of the patients had an elevated body temperature and 55% of the patients had tenderness over the lower abdomen (Table 1).Shigella flexneri (57%) and Shigella dysenteriae 1 (30%)were the most frequently isolated bacterial species in stool cultures. In vitro antibiotic resistance was greatest to tetra-643 on May 12, 2018 by guest http://aac.asm.org/ Downloaded from

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confidence: 99%

Comparative efficacies of pivmecillinam and ampicillin in acute shigellosis

Kabir¹,

Rahaman²,

Ahmed³

et al. 1984

Antimicrob Agents Chemother

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Section: Therapeutic Options and Their Limitationsmentioning

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“…Unfortunately, within 5 years of the inaugural RCT for shigellosis treatment, approximately 30% of isolated Shigella strains were resistant to ampicillin in certain areas of the United States. 20 Due to increased drug resistance and the failures of furazolidone and cephaloglycin in RCTs, the founding member of the quinolone class, nalidixic acid, was explored as a potential alternative. 21 While nalidixic acid treated children had worse clinical and bacteriological outcomes compared to ampicillin, it was still considered superior to placebo and selected as a potential therapeutic for children infected with Shigella resistant to ampicillin.…”

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Target Product Profile and Development Path for Shigellosis Treatment with Antibacterials

Arnold

2021

ACS Infect. Dis.

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Enteric infection with Shigella spp. can lead to symptoms ranging from acute watery diarrhea to sudden, severe dysentery. Approximately 212 000 diarrheal deaths annually are attributed to Shigella with a disproportionate impact in low-resource countries. The impact in under-resourced countries was illustrated by a reanalysis of the Global Enteric Multicenter Study which found that Shigella was the leading pathogen associated with moderate-to severe diarrhea in children under 5 years old. While recent studies have highlighted the burden of the disease, there has been a concurrent reduction in therapeutic options for the treatment of shigellosis as drug resistant strains increase in prevalence. In addition, increasing reports of drug resistant shigellosis cases in the men who have sex with men community confirm that the impact is not limited to low-resource countries. Despite the urgent need for new treatments, a target product profile (TPP) has not been established, and there is no clear development path for antibacterial treatments. To address this troubling concern, this manuscript describes a TPP for antishigellosis small molecule therapeutics and a development path that integrates currently available preclinical and clinical models of Shigella infection.

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“…This has been due to a rise in strains, particularly Shigella sonnei, with multiple antibiotic resistance patterns that included ampicillin (1)(2)(3)(4)(6)(7)(8)(9). Once ampicillin resistance has reached a high level, it has remained predominant.…”

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confidence: 99%